Project 1 In Conte Center Project 1, we will work to understand how cells of the central nervous system regulate the expression of complement and other immune proteins, and the extent to which this regulation is coupled to function and dysfunction at synapses. We will pursue these questions through experiments on clinical, post mortem, and biological samples. We will determine how the expression of C4A and C4B is regulated by allelic variation, cell type, and upstream biology (Aim 1). We will describe at single-cell resolution how diverse CNS cell types respond to synaptic dysfunction, utilizing the Drop-seq technology we developed to analyzed transcriptional responses in tens of thousands of individual cells (Aim 2). Finally, we will carefully evaluate cerebrospinal fluid as a potential reservoir of information about neural-immune interactions in the CNS (Aim 3). Through this work, we hope to better understand how neural-immune interactions play out through gene expression and may become visible in a clinical context.